Analysis of hydrogen effects on oxidative stress defense mechanisms and redox dynamics in the brain

• Project/Area Number: 25350907
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: Nippon Medical School
• Principal Investigator: Nishimaki Kiyomi 日本医科大学, 先端医学研究所, マネージメントサポートスタッフ (00465345)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 酸化ストレス / 水素 / トランスジェニックマウス

Outline of Final Research Achievements

Accumulation of oxidative stress associated with aging is one of causative factors in the pathogenesis of major neurodegenerative diseases including Alzheimer’ and Parkinson diseases (AD and PD). In animal experiments using mitochondrial oxidative stress enhanced mice (DAL mouse), hydrogen molecules revealed that it is effective in removing oxidative stress associated with aging. In this study, we developed a transgenic mouse that can quantitatively evaluate the oxidative stress in the body and crossed with DAL mouse. We tried to visualize removal of oxidative stress using this double transgenic mouse.

Research Products

• [Journal Article] Molecular hydrogen regulates gene expression by modifying the free radical chain reaction-dependent generation of oxidized phospholipid mediators. (2016)
  • Author(s): Iuchi K, Imoto A, Kamimura N, Nishimaki K, Ichimiya H, Yokota T, Ohta S.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 18971-18971
  • DOI: 10.1038/srep18971
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Oxidative stress accelerates amyloid deposition and memory impairment in a double-transgenic mouse model of Alzheimer's disease. (2015)
  • Author(s): Kanamaru T, Kamimura N, Yokota T, Iuchi K, Nishimaki K, Takami S, Akashiba H, Shitaka Y, Katsura K, Kimura K, Ohta S.
  • Journal Title: Neurosci Lett. Volume: 587 Pages: 126-131
  • DOI: 10.1016/j.neulet.2014.12.033
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Intravenous transplantation of bone marrow-derived mononuclear cells prevents memory impairment in transgenic mouse models of Alzheimer's disease. (2015)
  • Author(s): Kanamaru T, Kamimura N, Yokota T, Nishimaki K, Iuchi K, Lee H, Takami S, Akashiba H, Shitaka Y, Ueda M, Katsura K, Kimura K, Ohta S.
  • Journal Title: Brain Res. Volume: 1605 Pages: 49-58
  • DOI: 10.1016/j.brainres.2015.02.011
  • Peer Reviewed / Open Access
• [Journal Article] Real-Time Monitoring of Oxidative Stress in Live Mouse Skin (2014)
  • Author(s): Wolf AM, Nishimaki K, Kamimura N, Ohta S
  • Journal Title: J Invest Dermatol Volume: 34(6) Issue: 6 Pages: 1701-1709
  • DOI: 10.1038/jid.2013.428
  • Peer Reviewed
• [Journal Article] Preventive effects of Chlorella on skeletal muscle atrophy in muscle-specific mitochondrial aldehyde dehydrogenase 2 activity-deficient mice. (2014)
  • Author(s): Nakashima Y, Ohsawa I, Nishimaki K, Kumamoto S, Maruyama I, Suzuki Y, Ohta S
  • Journal Title: BMC Complement Altern Med Volume: 14 Issue: 1 Pages: 390-390
  • DOI: 10.1186/1472-6882-14-390
  • Peer Reviewed / Open Access
• [Presentation] 糖尿病モデルマウスのin vivo酸化還元状態の測定と分子状水素の効果 (2015)
  • Author(s): 上村尚美、Alexander M Wolf、一宮治美、井内勝哉、西槙貴代美、横田隆、太田成男
  • Organizer: 第38回日本分子生物学会 第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] 分子状水素はフリーラジカル連鎖反応で生じる脂質メディエイターを調節して遺伝子発現を制御する (2015)
  • Author(s): 井内勝哉、井本明美、西槙貴代美、一宮治美、Hyunjin Lee、横田隆、上村尚美、太田成男
  • Organizer: 第38回日本分子生物学会 第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] 糖尿病モデルマウスにおけるミトコンドリアのin vivo 酸化還元状態の測定と分子状水素の効果 (2015)
  • Author(s): 上村尚美、Alexander M Wolf、一宮治美、井内勝哉、西槙貴代美、横田隆、太田成男
  • Organizer: 第15回日本ミトコンドリア学会年会
  • Place of Presentation: 福井県立国際交流会館
  • Year and Date: 2015-11-19
• [Presentation] Drinking effect of hydrogen water prevents progression of Alzheimer's disease. (2015)
  • Author(s): Kiyomi Nishimaki, Takashi Yokota, Naomi Kamimura, Ikuroh Ohsawa, Shigeo Ohta
  • Organizer: The 2015 Gordon Research Conference on Biology of Aging.
  • Place of Presentation: Sunday River, USA
  • Year and Date: 2015-07-19
  • Int'l Joint Research
• [Presentation] Molecular hydrogen improves obesity and diabetes by regulating hepatic gene expression and stimulating energy metabolism in db/db mice (2015)
  • Author(s): Naomi Kamimura, Kiyomi Nishimaki, Harumi Ichimiya, Shigeo Ohta
  • Organizer: The 2015 Gordon Research Conference on Biology of Aging.
  • Place of Presentation: Sunday River, USA
  • Year and Date: 2015-07-19
  • Int'l Joint Research
• [Presentation] 低濃度の分子状水素はフリーラジカル連鎖反応に介入してシグナル伝達と遺伝子発現を制御する。 (2015)
  • Author(s): (1)井内勝哉、井本明美、上村尚美、西槙貴代美、一宮治美、太田成男
  • Organizer: 第5回分子状水素医学シンポジウム
  • Place of Presentation: 名古屋（ウインクあいち）
  • Year and Date: 2015-03-22
• [Presentation] Trancegenic mice expressing the redox-sensitive green fluorescent protein in the cytosol and mitochondria. (2014)
  • Author(s): Kiyomi Nishimaki, Alexander M Wolf , Takashi Yokota, Naomi Kamimura and Shigeo Ohta
  • Organizer: International meeting of mitochondrial pathology.
  • Place of Presentation: Tampere Finland
  • Year and Date: 2014-06-15 – 2014-06-19
• [Presentation] アルツハイマー病モデルマウスに対する骨髄単核球移植の予防・治療効果 (2013)
  • Author(s): 上村尚美、西槙貴代美、金丸拓也、横田隆、井内勝哉、高見新也、赤芝洋紀、志鷹義嗣、桂研一郎、片山泰朗、太田成男
  • Organizer: 第36回日本分子生物学会
  • Place of Presentation: 神戸国際会議場
• [Presentation] Accelerated Alzheimer-type Phenotype in transgenic mice carrying both mutant amyloid precursor protein and dominant-negative form of mitochondrial aldehyde dehydrogenase 2 (2013)
  • Author(s): Naomi Kamimura, Kiyomi Nishimaki,Takuya Kanamaru, Takashi Yokota, Katsuya Iuchi, Shinya Takami, Hiroki Akashiba, Yoshitsugu Shitaka, Ken-ichiro Katsura, Yasuo Katayama, and Shigeo Ohta
  • Organizer: International Symposium on Mitochondria 2013
  • Place of Presentation: 東京(六本木ヒルズ）
• [Presentation] 低濃度の分子状水素による連鎖的脂質過酸化の抑制効果
  • Author(s): 井内勝哉、西槙貴代美、井本明美、一宮治美、李 炫溱、上村尚美、太田成男
  • Organizer: 第４回分子状水素医学シンポジウム
  • Place of Presentation: 東京（品川区きゅりあん）
• [Remarks] 日本医科大学先端医学研究所 細胞生物学
  • URL: http://home.nms.ac.jp/ig/saiboseibutsu/index.html
• [Remarks] 日本医科大学 先端医学研究所 細胞生物学部門
  • URL: http://home.nms.ac.jp/ig/saiboseibutsu/index.html
• [Remarks] 日本医科大学老人病研究所 細胞生物学ホームページ
  • URL: http://home.nms.ac.jp/ig/saiboseibutsu/kenkyu.html